Our general goals have been to develop ultrasonic instrumentation, transducers, and techniques for evaluation of cardiovascular physiology and function in man and in animal models of human diseases and conditions, and recently we have been directing our efforts toward applications in mice where high spatial and temporal resolutions are critical. The unifying theme is the development of enabling technology consisting of simple, noninvasive methods which can be used by investigators to follow cardiovascular responses longitudinally as models develop, mature, and respond to challenges, and to quickly screen large numbers of mice. In this renewal we propose the following specific aims: 1) Develop a multichannel, multigate, multifrequency DC coupled pulsed Doppler mainframe and modules for measuring blood velocity and/or tissue motion in central (heart and aorta) and peripheral (carotid and coronary) arteries of mice. 2) Develop and optimize signal processing to acquire, process, display, and generate waveforms and indices from multiple velocity and dimension signals taken simultaneously. 3) Perfect a dual-velocity method to assess segmental arterial volume pulsations. 4) Use velocity and diameter signals to characterize arterial wave propagation, mechanics, and reflections. 5) Study coronary flow velocity waveforms and reserve and validate the use of isoflurane as a coronary vasodilator in several mouse models. The sensors, instrumentation, signal processing, and algorithms will permit noninvasive serial measurements to be made in normal and genetically engineered mice during growth, maturation, and development with the potential for rapid screening. When validated in mice, many of the general concepts may have diagnostic applications in man and could be incorporated into clinical ultrasound scanners. PUBLIC HEALTH RELEVANCE: Mice are being used in medical research to study how genes control the structure and operation of the heart and blood vessel and how aging and human-like diseases affect their function. Because the mouse heart is the size of a small peanut and beats very fast, it is difficult to make images, to detect blockages in vessels, or to take detailed measurements of heart contraction and motion using standard methods. Our goal is to develop and improve high resolution ultrasonic sensors and devices to measure blood flow and motion in the very small hearts and blood vessels of mice used in medical research.